An epigenetic tipping point in cancer comes under the microscope

Sroka, Martyna W.; Vakoc, Christopher R.

doi:10.1038/d41586-021-00002-5

Cited by 3 publications

(2 citation statements)

References 10 publications

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“… 287 This process, in which various chemical groups are covalently added to, or removed from, the DNA bases and the tails of the histones is referred to as epigenetic modifications. 288 Amplification of NSD3 and its immediate neighbors (e.g., FGFR1 ), located on the chromosomal region 8p11-12, is one of the frequent molecular alterations in LSCC 289 and has been implicated in the etiology of LSCC. 290 , 291 In contrast to FGFR1 , gene amplification of NSD3 correlates strongly with increased mRNA expression.…”

Section: Epigenetic Therapeutic Targets In Lsccmentioning

confidence: 99%

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Niu

Jin

Zhang

et al. 2022

Sig Transduct Target Ther

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Lung cancer is the leading cause of cancer-related death across the world. Unlike lung adenocarcinoma, patients with lung squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved cancer patients’ outcomes, the relatively low response rate and severe adverse events hinder the clinical application of this promising treatment in LSCC. Therefore, it is of vital importance to have a better understanding of the mechanisms underlying the pathogenesis of LSCC as well as the inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions for LSCC. In this review, new insights were given about classical signaling pathways which have been proved in other cancer types but not in LSCC, including PI3K signaling pathway, VEGF/VEGFR signaling, and CDK4/6 pathway. Other signaling pathways which may have therapeutic potentials in LSCC were also discussed, including the FGFR1 pathway, EGFR pathway, and KEAP1/NRF2 pathway. Next, chromosome 3q, which harbors two key squamous differentiation markers SOX2 and TP63 is discussed as well as its related potential therapeutic targets. We also provided some progress of LSCC in epigenetic therapies and immune checkpoints blockade (ICB) therapies. Subsequently, we outlined some combination strategies of ICB therapies and other targeted therapies. Finally, prospects and challenges were given related to the exploration and application of novel therapeutic strategies for LSCC.

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Section: Epigenetic Therapeutic Targets In Lsccmentioning

confidence: 99%

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Niu

Jin

Zhang

et al. 2022

Sig Transduct Target Ther

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“…This study emphasizes the usefulness of 1 H CS information in understanding and eventually refining protein‐ligand complex structures in solution. We chose the PWWP1 domain of the histone‐lysine N‐methyltransferase NSD3, a protein implicated in several forms of cancer, [19] as a model system. Potent NSD3 inhibitors binding to the PWWP1 domain have been recently reported [20] .…”

Section: Introductionmentioning

confidence: 99%

Ligand ¹H NMR Chemical Shifts as Accurate Reporters for Protein‐Ligand Binding Interfaces in Solution**

Platzer,

Ptaszek,

Böttcher

et al. 2023

ChemPhysChem

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The availability of high‐resolution 3D structural information is crucial for investigating guest‐host systems across a wide range of fields. In the context of drug discovery, the information is routinely used to establish and validate structure‐activity relationships, grow initial hits from screening campaigns, and to guide molecular docking. For the generation of protein‐ligand complex structural information, X‐ray crystallography is the experimental method of choice, however, with limited information on protein flexibility. An experimentally verified structural model of the binding interface in the native solution‐state would support medicinal chemists in their molecular design decisions. Here we demonstrate that protein‐bound ligand 1H NMR chemical shifts are highly sensitive and accurate probes for the immediate chemical environment of protein‐ligand interfaces. By comparing the experimental ligand 1H chemical shift values with those computed from the X‐ray structure using quantum mechanics methodology, we identify significant disagreements for parts of the ligand between the two experimental techniques. We show that quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) ensembles can be used to refine initial X‐ray co‐crystal structures resulting in a better agreement with experimental 1H ligand chemical shift values. Overall, our findings highlight the usefulness of ligand 1H NMR chemical shift information in combination with a QM/MM MD workflow for generating protein‐ligand ensembles that accurately reproduce solution structural data.

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Computational Study of Methionine Methylation Process Catalyzed by SETD3

Zhao

Deng

Rahman

et al. 2022

Interdiscip Sci Comput Life Sci

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An epigenetic tipping point in cancer comes under the microscope

Cited by 3 publications

References 10 publications

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Ligand ¹H NMR Chemical Shifts as Accurate Reporters for Protein‐Ligand Binding Interfaces in Solution**

Computational Study of Methionine Methylation Process Catalyzed by SETD3

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An epigenetic tipping point in cancer comes under the microscope

Cited by 3 publications

References 10 publications

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Ligand 1H NMR Chemical Shifts as Accurate Reporters for Protein‐Ligand Binding Interfaces in Solution**

Computational Study of Methionine Methylation Process Catalyzed by SETD3

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Product

Resources

About

Ligand ¹H NMR Chemical Shifts as Accurate Reporters for Protein‐Ligand Binding Interfaces in Solution**